Androgens are used in hormonal therapy. Androgens are administered as part of any hormonally-based male contraceptive since suppression of the hypophyseal-gonadal axis by progestational steroids or analogs of GnRH (gonadotropin releasing hormone) affects both the gametogenic and endocrine function of the testis. Androgens are indicated in the treatment of hypogonadism irrespective of the cause and have become the subject of intense interest in hormone replacement therapy (HRT) for both men and women.
The principal male hormone, testosterone, is responsible for the development of the male body habitus, secondary sexual characteristics, libido and potentia as well as the processes of spermatogenesis. Testosterone is a steroid produced by the testis and exhibits an extremely short half-life. It is only weakly active by oral administration. Consequently, the natural hormone finds limited use in therapeutic medicine where androgen supplementation is desired.
A number of synthetic androgens have been prepared over the last fifty years including esters of the free alcohol which exhibit varying durations of activity following a single intramuscular injection. Notable among these is testosterone enanthate, which is used extensively for replacement therapy in hypogonadal men and as the androgenic component of several experimental male contraceptives. However, it must be administered at biweekly intervals in order to maintain testosterone levels in the normal range. Other 17-esters of testosterone are being developed as a long-acting injectable androgen. Like testosterone enanthate, these products are administered in an oily vehicle and have limited duration of action.
The development of oral formulations of androgenic steroids has been less successful. The most widely used commercial preparation is methyltestosterone which unfortunately, is associated with hepatotoxicity upon chronic administration. Therapeutic uses of androgens for replacement therapy usually require long-term treatment, thus precluding utilization of 17-alkylated steroids with their associated toxicity. Testosterone undecanoate also has been marketed as an oral androgen but, like testosterone, it is rapidly metabolized by the liver and must be administered several times a day, which may be inconvenient to the patient.
The foregoing shows that there exists a need for androgenic agents with long-acting activity, particularly long-acting oral activity. The advantages of the invention, as well as inventive features, will be apparent from the description of the invention provided herein.